A nicotine vaccine (NincVax or 3'-immunogen) has been developed which elicits high titers of nicotine-specific antibodies in experimental animals. Immunization of rats substantially reduces the fraction of a nicotine dose reaching the brain, prevents nicotine-induced increases in blood pressure, prevents nicotine-induced stimulation of locomoter activity, and inhibits the relief of mediated behaviors relevant to nicotine dependence. These effects are observed at clinically relevant nicotine doses, and with nicotine-specific IgG titers that should be achievable in humans. The current proposal is one of four components of this SPIRCAP application, the purpose of which is to perform late preclinical and human clinical studies evaluating vaccination against nicotine as a potential treatment for nicotine dependence. The individual and human clinical studies evaluating vaccination against nicotine as a potential treatment for nicotine dependence. The individual components of the SPIRCAP application are 1) Development and manufacturing for clinical studies and serological testing (Dr. Fattom, Nabi, Rockville), 2) Behavioral studies of vaccination in rats (Dr. Malin, U. Houston-Clear Lake), 3) Pharmacokinetic and additional behavioral studies of vaccination in rats (Dr. Pentel, Minneapolis Medical Research Foundation) and 4) Phase I/II and III clinical trials of vaccination (Dr. Hatsukami, U. Minnesota). An Administrative Core will provide overall coordination and administrative support for the project (Dr. Scott Winston, Nabi, Rockville). In addition, toxicology studies of the nicotine vaccine will be performed under a separate contract with NIDA. The aims of this component of the SPIRCAP are to: 1) Manufacture two clinical lots of NicVax 2) Perform preclinical safety and toxicology studies 3) Prepare and submit IND for human clinical studies 4) Perform serological testing on preclinical and clinical samples 5) Conduct clinical site and data monitoring in support of the human clinical studies